Efforts to evaluate the relationship between genetic polymorphisms and susceptibilities to various types of cancers have intensified in recent years in the Department of Environmental Medicine and have resulted in successful collaborative NIH grant applications between investigators in the Epidemiology and Molecular Toxicology/Carcinogenesis Programs in the Department. Additionally, several members of the Department have long NIH funded track records in evaluating the epigenetic effects of DNA methylation at CpG islands in carcinogenesis models. Furthermore, increased efforts in these areas are reflected in Environmental Medicine's successful acquisition of a Superfund Basic Research Program Center Grant entitled "Genetic/Epigenetic Susceptibility to Superfund Chemicals." Other NIH funded projects by Department investigators involve the development of linkage maps with single nucleotide polymorphisms as markers to identify novel genes associated with toxicant induced disease. With this application, we propose to acquire a Pyrosequencer TM to be housed in the shared Molecular Facility Core of Environmental Medicine's longstanding NIEHS Center. This instrument is needed to increase the throughput and accuracy of genotyping for the multiple NIH funded genotyping studies by members of this Department. By increasing sample and loci number, these investigations will be much more sensitive in evaluating the effects of genetic polymorphisms on susceptibility to disease. Similarly, investigators studying the relationships between methylation status and carcinogenesis will be able to expand their analyses to include multiple CpG islands within a short stretch of DNA and will now be able to quantitatively estimate the percentage of hypermethylated nucleotides at individual islands. The NIH grant support obtained by the several research groups needing this instrument shows that they are conducting high-quality science; with the acquisition of the Pyrosequencer they will be able to perform more extensive and detailed investigations that will enable them to stay at the forefront in their research areas.